tbuckley/cabot-search huggingface dataset:
Systemic Therapy Update on <sup>177</sup>Lutetium-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer: ASCO Rapid Recommendation
Authors: Rohan Garje, R. Bryan Rumble, Rahul A. Parikh
Journal: Journal of Clinical Oncology (2022)

ASCO Rapid Recommendations Updates highlight revisions to select ASCO guideline recommendations as a response to the emergence of new and practice-changing data. The rapid updates are supported by an evidence review and follow the guideline development processes outlined in the ASCO Guideline Methodology Manual. The goal of these articles is to disseminate updated recommendations, in a timely manner, to better inform health practitioners and the public on the best available cancer care options.
Transposon Mutagenesis Reveals RBMS3 Silencing as a Promoter of Malignant Progression of BRAFV600E-Driven Lung Tumorigenesis
Authors: Aria Vaishnavi, Joseph Juan, Maebh Jacob, Christopher Stehn, Eric E. Gardner, Michael T. Scherzer, Sophia Schuman, J. Edward Van Veen, Brandon Murphy, Christopher S. Hackett, Adam J. Dupuy, Steven A. Chmura, Louise van der Weyden, Justin Y. Newberg, Annie Liu, Karen Mann, Alistair G. Rust, William A. Weiss, Conan G. Kinsey, David J. Adams, Allie Grossmann, Michael B. Mann, Martin McMahon
Journal: Cancer Research (2022)

Abstract Mutationally activated BRAF is detected in approximately 7% of human lung adenocarcinomas, with BRAFT1799A serving as a predictive biomarker for treatment of patients with FDA-approved inhibitors of BRAFV600E oncoprotein signaling. In genetically engineered mouse (GEM) models, expression of BRAFV600E in the lung epithelium initiates growth of benign lung tumors that, without additional genetic alterations, rarely progress to malignant lung adenocarcinoma. To identify genes that cooperate with BRAFV600E for malignant progression, we used Sleeping Beauty–mediated transposon mutagenesis, which dramatically accelerated the emergence of lethal lung cancers. Among the genes identified was Rbms3, which encodes an RNA-binding protein previously implicated as a putative tumor suppressor. Silencing of RBMS3 via CRISPR/Cas9 gene editing promoted growth of BRAFV600E lung organoids and promoted development of malignant lung cancers with a distinct micropapillary architecture in BRAFV600E and EGFRL858R GEM models. BRAFV600E/RBMS3Null lung tumors displayed elevated expression of Ctnnb1, Ccnd1, Axin2, Lgr5, and c-Myc mRNAs, suggesting that RBMS3 silencing elevates signaling through the WNT/β-catenin signaling axis. Although RBMS3 silencing rendered BRAFV600E-driven lung tumors resistant to the effects of dabrafenib plus trametinib, the tumors were sensitive to inhibition of porcupine, an acyltransferase of WNT ligands necessary for their secretion. Analysis of The Cancer Genome Atlas patient samples revealed that chromosome 3p24, which encompasses RBMS3, is frequently lost in non–small cell lung cancer and correlates with poor prognosis. Collectively, these data reveal the role of RBMS3 as a lung cancer suppressor and suggest that RBMS3 silencing may contribute to malignant NSCLC progression. Significance: Loss of RBMS3 cooperates with BRAFV600E to induce lung tumorigenesis, providing a deeper understanding of the molecular mechanisms underlying mutant BRAF-driven lung cancer and potential strategies to more effectively target this disease.
Fix it and feel free to work: endoscopy beside the stent
Authors: Antonino Granata, Giacomo E. M. Rizzo, Giuseppe Nicosia, Leo Licari, Cosimo Callari, Mario Traina
Journal: Endoscopy (2022)

A 45-year-old man underwent bariatric surgery (gastric bypass with Roux-en-Y anastomosis) and subsequently developed an anastomotic leak with an intra-abdominal fluid collection and septic status. He underwent a reintervention with complete washing of the cavity, insertion of abdominal drainage, and placement of a percutaneous surgical gastrostomy in the excluded stomach. However, he showed no clinical improvement after 2 weeks and was referred to our institution for endoscopic treatment.
Palliative Care Early in the Care Continuum among Patients with Serious Respiratory Illness: An Official ATS/AAHPM/HPNA/SWHPN Policy Statement
Authors: Donald R. Sullivan, Anand S. Iyer, Susan Enguidanos, Christopher E. Cox, Morag Farquhar, Daisy J. A. Janssen, Kathleen O. Lindell, Richard A. Mularski, Natasha Smallwood, Alison E. Turnbull, Anne M. Wilkinson, Katherine R. Courtright, Matthew Maddocks, Mary Lynn McPherson, J. Daryl Thornton, Margaret L. Campbell, Tracy K. Fasolino, Patricia M. Fogelman, Larry Gershon, Thayer Gershon, Christiane Hartog, Judy Luther, Diane E. Meier, Judith E. Nelson, Elliot Rabinowitz, Cynda H. Rushton, Danetta H. Sloan, Erin K. Kross, Lynn F. Reinke
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

Section:ChooseTop of pageAbstract <<IntroductionMethodsPalliative Care DomainsConclusionsReferencesCITING ARTICLES
Trainees face wait till January to sit exams after last minute cancellation for royal funeral
Authors: Adele Waters
Journal: BMJ (2022)

Morbidity and mortality increase when diastolic dysfunction accompanies coronary artery disease (CAD). An elevated stress <sup>201</sup>Tl lung-to-heart ratio (LHR) is a traditional marker of elevated left ventricular end-diastolic pressure (LVEDP), which adds prognostic value in CAD. Since the introduction of <sup>99m</sup>Tc-labeled agents, this valuable marker has been lost. Hence, there is only a limited ability to assess diastolic dysfunction by myocardial perfusion imaging (MPI). <b>Methods:</b> Fifty-two consecutive patients with an ejection fraction of ≥45% underwent MPI and cardiac catheterization within 15 d. Peak filling rate (PFR), time to PFR (TPFR), and filling rate during the first third of diastole (1/3FR) were obtained from MPI with SPECT software. Resting <sup>201</sup>Tl LHR was calculated manually, and LVEDP was obtained at catheterization. <b>Results:</b> PFR, TPFR, and 1/3FR correlated significantly with LVEDP (<i>r =</i> −0.53, 0.45, and −0.45, respectively; <i>P =</i> 0.00005, 0.0009, and 0.0009, respectively), whereas resting <sup>201</sup>Tl LHR did not (<i>r</i> = 0.10, <i>P</i> = 0.49). Receiver-operating-characteristic curve analysis of PFR, TPFR, and 1/3FR for detecting LVEDPs of ≥18 mm Hg showed areas under the curve of 0.83, 0.75, and 0.80, respectively. The combination of PFR and 1/3FR showed a negative predictive value of 84%, a positive predictive value of 86%, and a specificity of 94%. <b>Conclusion:</b> Diastolic filling variables obtained with the SPECT software showed a significant correlation with LVEDP. PFR, TPFR, and 1/3FR were superior to resting <sup>201</sup>Tl LHR and showed good sensitivity, specificity, and predictive power for detecting LVEDPs of ≥18 mm Hg. Hence, combining data on the presence of perfusion defects with data on diastolic impairments can be achieved by adding these variables to MPI results.
Adjuvant Chemotherapy for Breast Cancer
Authors: Aman U. Buzdar
Journal: JAMA (1986)

<h3>To the Editor.—</h3> The National Institutes of Health CONSENSUS CONFERENCE, "Adjuvant Chemotherapy for Breast Cancer,"<sup>1</sup>was prepared based on extensive review of adjuvant therapy trials. For patients younger than 50 years of age with positive nodes, regardless of estrogen receptor status, combination chemotherapy was recommended as the treatment of choice. The effectiveness of combination chemotherapy in this group has been well established, and most individual studies have shown a significant reduction in mortality. Results of therapy for patients 50 years of age or older were somewhat less conclusive. For those patients with involved nodes and estrogen receptor-positive tumors not participating in clinical trials, the panel recommended tamoxifen as the treatment of choice. We are concerned with the use of "treatment of choice" in the recommendation. This recommendation was based on review of pooled data from approximately 12,000 patients treated at institutions throughout the world.<sup>2</sup>The review suggested an
The 5th Edition of the World Health Organization Classification of Hematolymphoid Tumors
Authors: Weijie Li
Journal: Leukemia (2022)

The WHO classification of tumors of various organ systems, also known as the WHO Blue Books, has provided a unified tumor classification system enabling people across the world to share their knowledge and research results. Newer editions with updates have been made every five to ten years to reflect our better understanding of these diseases through the ongoing research work conducted by many researchers and physicians. The last edition of the WHO classification of hematolymphoid tumors was the 4th edition released in 2008 and revised in 2017. Recently, the 5th edition of the WHO classification of hematolymphoid tumors was released, with the online version available since August 2022, and the print version expected to be out at the end of 2022. The 5th edition has been completely rewritten with numerous changes and updates, which include revised hierarchical classification structure, addition or deletion of entities or subtypes, changes or revisions of terminology or nomenclature, revisions or changes of diagnostic criteria, and updates of pathogenesis, clinical and genetic features. Stroma-derived tumors of lymphoid tissue and tumor-like lesions have been included for the first time. This chapter provides a brief overview of the 5th edition of the WHO classification of hematolymphoid tumors with a focus on the changes and updates from a reader's perspective.
Chemically-induced osteogenic cells for bone tissue engineering and disease modeling
Authors: Ji-Young Yoon, Nandin Mandakhbayar, Jeongeun Hyun, Dong Suk Yoon, Kapil D. Patel, Keunsoo Kang, Ho-Shup Shim, Hae-Hyoung Lee, Jung-Hwan Lee, Kam W. Leong, Hae-Won Kim
Journal: Biomaterials (2022)
Covalent organic framework nanomedicines: Biocompatibility for advanced nanocarriers and cancer theranostics applications
Authors: Nem Singh, Jungryun Kim, Jaewon Kim, Kyungwoo Lee, Zehra Zunbul, Injun Lee, Eunji Kim, Sung-Gil Chi, Jong Seung Kim
Journal: Bioactive Materials (2022)

Nanomedicines for drug delivery and imaging-guided cancer therapy is a rapidly growing research area. The unique properties of nanomedicines have a massive potential in solving longstanding challenges of existing cancer drugs, such as poor localization at the tumor site, high drug doses and toxicity, recurrence, and poor immune response. However, inadequate biocompatibility restricts their potential in clinical translation. Therefore, advanced nanomaterials with high biocompatibility and enhanced therapeutic efficiency are highly desired to fast-track the clinical translation of nanomedicines. Intrinsic properties of nanoscale covalent organic frameworks (nCOFs), such as suitable size, modular pore geometry and porosity, and straightforward post-synthetic modification via simple organic transformations, make them incredibly attractive for future nanomedicines. The ability of COFs to disintegrate in a slightly acidic tumor microenvironment also gives them a competitive advantage in targeted delivery. This review summarizes recently published applications of COFs in drug delivery, photo-immuno therapy, sonodynamic therapy, photothermal therapy, chemotherapy, pyroptosis, and combination therapy. Herein we mainly focused on modifications of COFs to enhance their biocompatibility, efficacy and potential clinical translation. This review will provide the fundamental knowledge in designing biocompatible nCOFs-based nanomedicines and will help in the rapid development of cancer drug carriers and theranostics.
Promoting lacunar bone regeneration with an injectable hydrogel adaptive to the microenvironment
Authors: Ao Zheng, Xiao Wang, Xianzhen Xin, Lingjie Peng, Tingshu Su, Lingyan Cao, Xinquan Jiang
Journal: Bioactive Materials (2022)

Injectable hydrogel is suitable for the repair of lacunar bone deficiency. This study fabricated an injectable, self-adaptive silk fibroin/mesoporous bioglass/sodium alginate (SMS) composite hydrogel system. With controllable and adjustable physical and chemical properties, the SMS hydrogel could be easily optimized adaptively to different clinical applications. The SMS hydrogel effectively showed great injectability and shapeability, allowing defect filling with no gap. Moreover, the SMS hydrogel displayed self-adaptability in mechanical reinforcement and degradation, responsive to the concentration of Ca2+ and inflammatory-like pH value in the microenvironment of bone deficiency, respectively. In vitro biological studies indicated that SMS hydrogel could promote osteogenic differentiation of bone marrow mesenchymal stem cells by activation of the MAPK signaling pathway. The SMS hydrogel also could improve migration and tube formation of human umbilical vein endothelial cells. Investigations of the crosstalk between osteoblasts and macrophages confirmed that SMS hydrogel could regulate macrophage polarization from M1 to M2, which could create a specific favorable environment to induce new bone formation and angiogenesis. Meanwhile, SMS hydrogel was proved to be antibacterial, especially for gram-negative bacteria. Furthermore, in vivo study indicated that SMS could be easily applied for maxillary sinus elevation, inducing sufficient new bone formation. Thus, it is convincing that SMS hydrogel could be potent in a simple, minimally invasive and efficient treatment for the repair of lacunar bone deficiency.
Shifting focus from bacteria to host neutrophil extracellular traps of biodegradable pure Zn to combat implant centered infection
Authors: Feng Peng, Juning Xie, Haiming Liu, Yufeng Zheng, Xin Qian, Ruixiang Zhou, Hua Zhong, Yu Zhang, Mei Li
Journal: Bioactive Materials (2022)

The widespread use of orthopedic implants to support or replace bones is increasingly threatened by the risk of incurable bacterial infections, impenetrable microbial biofilms, and irreversible antibiotic resistance. In the past, the development of anti-infective biomaterials focused solely on direct antibacterial properties while ignoring the host's immune response. Inspired by the clearance of infection by the innate neutrophil response and participation in anti-infectious immunity of Zn ions, we report an innovative neutrophil extracellular traps (NETs) strategy, induced by biodegradable pure Zn, which achieved therapeutic efficacy toward biomaterial-related infections. Our
Passively-targeted mitochondrial tungsten-based nanodots for efficient acute kidney injury treatment
Authors: Qiong Huang, Yuqi Yang, Tianjiao Zhao, Qiaohui Chen, Min Liu, Shuting Ji, Yan Zhu, Yunrong Yang, Jinping Zhang, Haixin Zhao, Yayun Nan, Kelong Ai
Journal: Bioactive Materials (2022)

Acute kidney injury (AKI) can lead to loss of kidney function and a substantial increase in mortality. The burst of reactive oxygen species (ROS) plays a key role in the pathological progression of AKI. Mitochondrial-targeted antioxidant therapy is very promising because mitochondria are the main source of ROS in AKI. Antioxidant nanodrugs with actively targeted mitochondria have achieved encouraging success in many oxidative stress-induced diseases. However, most strategies to actively target mitochondria make the size of nanodrugs too large to pass through the glomerular system to reach the renal tubules, the main damage site of AKI. Here, an ultra-small Tungsten-based nanodots (TWNDs) with strong ROS scavenging can be very effective for treatment of AKI. TWNDs can reach the tubular site after crossing the glomerular barrier, and enter the mitochondria of the renal tubule without resorting to complex active targeting strategies. To our knowledge, this is the first time that ultra-small negatively charged nanodots can be used to passively target mitochondrial therapy for AKI. Through in-depth study of the therapeutic mechanism, such passive mitochondria-targeted TWNDs are highly effective in protecting mitochondria by reducing mitochondrial ROS and increasing mitophagy. In addition, TWNDs can also reduce the infiltration of inflammatory cells. This work provides a new way to passively target mitochondria for AKI, and give inspiration for the treatment of many major diseases closely related to mitochondria, such as myocardial infarction and cerebral infarction.
Abstract B030: Induction chemotherapy plus concurrent chemoradiotherapy led to clinical complete response in locally advanced sinonasal rhabdosarcomas
Authors: Qiuji Wu, Shaojie Li, Juan Wang, Jia Liu, Yahua Zhong
Journal: Clinical Cancer Research (2022)

Abstract Background: Sinonasal rhabdosarcoma is a rare but aggressive malignancy. In cases where locally advanced diseases involve critical structures such as the orbital and cranial cavities, surgery may not guarantee safety margin. Therefore, we evaluated the effect of induction chemotherapy plus concurrent chemoradiotherapy in locally advanced sinonasal rhabdosarcoma. Methods: During January 2013 to January 2019, 4 patients (2 males and 2 females, 22 to 33 years old) with locally advanced sinonasal rhabdosarcoma (3 alveolar and 1 poorly differentiated rhabdosarcoma) were treated with induction chemotherapy followed by concurrent radiochemotherapy. The patients were staged as cT4N0M0, cT4N0M0, cT4N1M0, and cT3N1M0 respectively. The patients were treated with induction chemotherapy composed of 2 to 4 cycles of EI regimen (epirubicin 60mg/m2, day 1-day 2; Ifosfamide 1.8g/m2, day 1-day 5; every 21 days) based on their tolerance. Thereafter, all patients received concurrent radiochemotherapy with 70Gy in 30 fractions given to the primary tumors and 63Gy in 30 fractions to the lymph nodes in N1 patients. Concurrent chemotherapy with cisplatin (100mg/m2, day 1 and day 22) was delivered during the course of radiotherapy. The follow-up time was 29, 28, 7 and 4 months, respectively. Results: Induction chemotherapy yielded partial response and concurrent radiochemotherapy led to clinical complete response. No sign of local recurrence was detected until the last follow-up. Only one patient had vertebral metastasis 6 months post-treatment in T10 and received vertebral irradiation. Others were free of distant metastasis. During the induction chemotherapy, all patients were presented with grade IV leucopenia, 3 of whom developed febrile neutropenia that required dose reduction in the consecutive chemotherapies. Concurrent radiochemotherapy was well tolerated, 3 patients developed grade II leucopenia and 1 grade IV leucopenia. All patients experienced grade II gastrointestinal side effects, dermatitis, and stomatitis. Conclusions: Induction chemotherapy plus concurrent chemoradiotherapy could lead to clinical complete response in locally advanced sinonasal rhabdosarcoma. Hematological toxicities were the most common toxicities and should be monitored and treated carefully. Longer follow-up and larger scale of study are needed to confirm these results. Citation Format: Qiuji Wu, Shaojie Li, Juan Wang, Jia Liu, Yahua Zhong. Induction chemotherapy plus concurrent chemoradiotherapy led to clinical complete response in locally advanced sinonasal rhabdosarcomas [abstract]. In: Proceedings of the AACR Special Conference: Sarcomas; 2022 May 9-12; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2022;28(18_Suppl):Abstract nr B030.
YAP/Smad3 promotes pathological extracellular matrix microenviroment‐induced bladder smooth muscle proliferation in bladder fibrosis progression
Authors: Xing‐Peng Di, Xi Jin, Jian‐Zhong Ai, Li‐Yuan Xiang, Xiao‐Shuai Gao, Kai‐Wen Xiao, Hong Li, De‐Yi Luo, Kun‐Jie Wang
Journal: MedComm (2022)

Fibrosis is a chronic inflammation process with excess extracellular matrix (ECM) deposition that cannot be reversed. Patients suffer from bladder dysfunction caused by bladder fibrosis. Moreover, the interactive mechanisms between ECM and bladder fibrosis are still obscure. Hence, we assessed the pivotal effect of Yes-associated protein (YAP) on the proliferation of bladder smooth muscle in fibrosis process. We identified that stiff ECM increased the expression and translocation of YAP in the nucleus of human bladder smooth muscle cell (hBdSMC). Sequencings and proteomics revealed that YAP bound to Smad3 and promoted the proliferation of hBdSMC via MAPK/ERK signaling pathway in stiff ECM. Moreover, CUT and TAG sequencing and dual-luciferase assays demonstrated that Smad3 inhibited the transcription of JUN. The YAP inhibitor CA3 was used in a partial bladder outlet obstruction (pBOO) rat model. The results showed that CA3 attenuated bladder smooth muscle proliferation. Collectively, YAP binding with Smad3 in the nucleus inhibited the transcription of JUN, and promoted the proliferation of bladder smooth muscle through the MAPK/ERK signaling pathway. The current study identified a novel mechanism of mechanical force induced bladder fibrosis that provided insights in YAP-associated organ fibrosis.
Gene-based Confirmatory Germline Testing Following Tumor-only Sequencing of Prostate Cancer
Authors: Hong Truong, Kelsey Breen, Subhiksha Nandakumar, Daniel D. Sjoberg, Yelena Kemel, Nikita Mehta, Andrew T. Lenis, Peter A. Reisz, Jessica Carruthers, Nicole Benfante, Vijai Joseph, Aliya Khurram, Anuradha Gopalan, Samson W. Fine, Victor E. Reuter, Andrew J. Vickers, Ozge Birsoy, Ying Liu, Michael Walsh, Alicia Latham, Diana Mandelker, Zsofia K. Stadler, Eugene Pietzak, Behfar Ehdaie, Karim A. Touijer, Vincent P. Laudone, Susan F. Slovin, Karen A. Autio, Daniel C. Danila, Dana E. Rathkopf, James A. Eastham, Yu Chen, Michael J. Morris, Kenneth Offit, David B. Solit, Howard I. Scher, Wassim Abida, Mark E. Robson, Maria I. Carlo
Journal: European Urology (2022)
Bioinspired drug-delivery system emulating the natural bone healing cascade for diabetic periodontal bone regeneration
Authors: He Wang, Xiaowei Chang, Qian Ma, Boyang Sun, Han Li, Jinmin Zhou, Yiyao Hu, Xiaoyu Yang, Jie Li, Xin Chen, Jinlin Song
Journal: Bioactive Materials (2022)

Diabetes mellitus (DM) aggravates periodontitis, resulting in accelerated periodontal bone resorption. Disordered glucose metabolism in DM causes reactive oxygen species (ROS) overproduction resulting in compromised bone healing, which makes diabetic periodontal bone regeneration a major challenge. Inspired by the natural bone healing cascade, a mesoporous silica nanoparticle (MSN)-incorporated PDLLA (poly(dl-lactide))-PEG-PDLLA (PPP) thermosensitive hydrogel with stepwise cargo release is designed to emulate the mesenchymal stem cell "recruitment-osteogenesis" cascade for diabetic periodontal bone regeneration. During therapy, SDF-1 quickly escapes from the hydrogel due to diffusion for early rat bone marrow stem cell (rBMSC) recruitment. Simultaneously, slow degradation of the hydrogel starts to gradually expose the MSNs for sustained release of metformin, which can scavenge the overproduced ROS under high glucose conditions to reverse the inhibited osteogenesis of rBMSCs by reactivating the AMPK/β-catenin pathway, resulting in regulation of the diabetic microenvironment and facilitation of osteogenesis. In vitro experiments indicate that the hydrogel markedly restores the inhibited migration and osteogenic capacities of rBMSCs under high glucose conditions. In vivo results suggest that it can effectively recruit rBMSCs to the periodontal defect and significantly promote periodontal bone regeneration under type 2 DM. In conclusion, our work provides a novel therapeutic strategy of a bioinspired drug-delivery system emulating the natural bone healing cascade for diabetic periodontal bone regeneration.